The purpose of this project is to determine the objective clinical response rate of TIL therapy in HPV-positive cancers and to investigate the specificity, phenotype, and function of TIL from HPV-positive cancers in vitro and in vivo. Our laboratory has established the feasibility of generating TIL from HPV-positive cancers at clinical grade and scale. Based on that work we have conducted a clinical trial of TIL from HPV-positive cancers (HPV-TIL). Laboratory studies to characterize HPV-TIL and to innovate the next generate of cellular therapies for this family of diseases are ongoing. We have reported in the Journal of Clinical Oncology that complete tumor regression occurred in 2/9 women with cervical cancer treated on this protocol. This study was the first and only study thus far to demonstrate complete regression of an epithelial cancer following adoptive T-cell therapy. We have also reported in Science that durable, complete tumor responses in this clinical trial were linked to the targeting of HPV and non-HPV antigens. This finding changes the paradigm for immunotherapy of HPV+ cancers to emphasize the potential importance of non-viral antigen targets.